Please use this identifier to cite or link to this item: https://doi.org/10.3390/cancers11060836
Title: FBXW5 Promotes Tumorigenesis and Metastasis in Gastric Cancer via Activation of the FAK-Src Signaling Pathway
Authors: Yeo
Subhash
KAZUTO SUDA 
HAYRI EMRAH BALCIOGLU 
ZHOU SIQIN 
THUYA WIN LWIN 
LOH XIN YI 
Jammula
PRAVEEN CHAKRAVARTHY PEETHALA 
Tan
Xie
Wong
Ladoux,Benoit 
Ito
YANG HE 
Goh
Wang
YONG WEI PENG 
Issue Date: 2019
Publisher: MDPI AG
Citation: Yeo, Subhash, KAZUTO SUDA, HAYRI EMRAH BALCIOGLU, ZHOU SIQIN, THUYA WIN LWIN, LOH XIN YI, Jammula, PRAVEEN CHAKRAVARTHY PEETHALA, Tan, Xie, Wong, Ladoux,Benoit, Ito, YANG HE, Goh, Wang, YONG WEI PENG (2019). FBXW5 Promotes Tumorigenesis and Metastasis in Gastric Cancer via Activation of the FAK-Src Signaling Pathway. Cancers 11 (6) : 836-836. ScholarBank@NUS Repository. https://doi.org/10.3390/cancers11060836
Abstract: F-box/WD repeat-containing protein 5 (FBXW5) is a member of the FBXW subclass of F-box proteins. Despite its known function as a component of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex, the role of FBXW5 in gastric cancer tumorigenesis and metastasis has not been investigated. The present study investigates the role of FBXW5 in tumorigenesis and metastasis, as well as the regulation of key signaling pathways in gastric cancer; using in-vitro FBXW5 knockdown/overexpression cell line and in-vivo models. In-vitro knockdown of FBXW5 results in a decrease in cell proliferation and cell cycle progression, with a concomitant increase in cell apoptosis and caspase-3 activity. Furthermore, knockdown of FBXW5 also leads to a down regulation in cell migration and adhesion, characterized by a reduction in actin polymerization, focal adhesion turnover and traction forces. This study also delineates the mechanistic role of FBXW5 in oncogenic signaling as its inhibition down regulates RhoA-ROCK 1 (Rho-associated protein kinase 1) and focal adhesion kinase (FAK) signaling cascades. Overexpression of FBXW5 promotes in-vivo tumor growth, whereas its inhibition down regulates in-vivo tumor metastasis. When considered together, our study identifies the novel oncogenic role of FBXW5 in gastric cancer and draws further interest regarding its clinical utility as a potential therapeutic target.
Source Title: Cancers
URI: https://scholarbank.nus.edu.sg/handle/10635/155743
ISSN: 2072-6694
DOI: 10.3390/cancers11060836
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